MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, 90 High Holborn 2nd Floor, London, WC1V 6LJ, UK.
Research Division, Vital Strategies, New York, USA.
Trials. 2022 Jun 7;23(1):474. doi: 10.1186/s13063-022-06397-4.
Results from the STREAM stage 1 trial showed that a 9-month regimen for patients with rifampicin-resistant tuberculosis was non-inferior to the 20-month regimen recommended by the 2011 WHO treatment guidelines. Similar levels of severe adverse events were reported on both regimens suggesting the need for further research to optimise treatment. Stage 2 of STREAM evaluates two additional short-course regimens, both of which include bedaquiline. Throughout stage 2 of STREAM, new drug choices and a rapidly changing treatment landscape have necessitated changes to the trial's design to ensure it remains ethical and relevant. This paper describes changes to the trial design to ensure that stage 2 continues to answer important questions. These changes include the early closure to recruitment of two trial arms and an adjustment to the definition of the primary endpoint. If the STREAM experimental regimens are shown to be non-inferior or superior to the stage 1 study regimen, this would represent an important contribution to evidence about potentially more tolerable and more efficacious MDR-TB regimens, and a welcome advance for patients with rifampicin-resistant tuberculosis and tuberculosis control programmes globally.Trial registration: ISRCTN ISRCTN18148631 . Registered 10 February 2016.
STREAM 阶段 1 试验的结果表明，与 2011 年世卫组织治疗指南推荐的 20 个月疗程相比，耐利福平结核病患者的 9 个月疗程并不差。两种方案报告的严重不良事件水平相似，这表明需要进一步研究以优化治疗。STREAM 的第二阶段评估了另外两种短期疗程方案，这两种方案都包括贝达喹啉。在 STREAM 的第二阶段，新的药物选择和快速变化的治疗环境要求对试验设计进行更改，以确保其仍然符合伦理和相关性。本文介绍了试验设计的更改，以确保第二阶段继续回答重要问题。这些变化包括提前关闭两个试验臂的招募和对主要终点定义的调整。如果 STREAM 实验方案被证明与第一阶段研究方案不劣效或更优效，这将是对潜在更耐受和更有效的耐多药结核病方案的重要贡献，也是对全球耐利福平结核病患者和结核病控制规划的一个受欢迎的进展。
ISRCTN ISRCTN18148631。于 2016 年 2 月 10 日注册。
